tbuckley/cabot-search huggingface dataset:
Concordance of genomic alterations in anal cancer by next-generation sequencing in tissue and circulating tumor DNA.
Authors: Michael Brian LaPelusa, Christopher G Cann, Cathy Eng
Journal: Journal of Clinical Oncology (2023)

2 Background: The feasibility of identifying genomic alterations via next-generation sequencing (NGS) of peripheral blood (PB) to spare patients an invasive biopsy is an active area of investigation. High concordance of mutations between tissue and PB has been observed in several cancer types. However, the concordance between tissue and PB in patients with SCCA is unknown. Methods: We identified 11 patients with SCCA who had NGS (TEMPUS) performed on tissue and PB between 2017 - 2022. The IRB at Vanderbilt-Ingram Cancer Center approved this study. Results: See Table. Conclusions: In 6 of the 11 patients, concordant genomic alterations found in tissue were also identified in PB. More patients with anal cancer should be studied to better understand this phenomenon and the impact of therapy on ctDNA kinetics.[Table: see text]
Predicting recurrence in patients with stage II and III colon cancer: Validation cohort and long-term follow-up of the experimental cohort.
Authors: David Viñal, Daniel Martinez-Perez, Sergio Martínez-Recio, Laura Gutiérrez-Sainz, Iciar Ruiz-Gutierrez, Diego Jiménez-Bou, Jesus Peña-Lopez, Maria Alameda-Guijarro, Gema Martin-Montalvo, Antonio Rueda-Lara, Andrea Garcia-Leal, Patricia Zwisler, Maria Elena Palacios, Ana B. Custodio, Jaime Feliu, Nuria Rodriguez Salas, Ismael Ghanem
Journal: Journal of Clinical Oncology (2023)

215 Background: The prognosis of stage II and III colon cancer is heterogeneous and current staging system do not accurately predict recurrence. We previously reported a score that was able to select a subgroup of patient with excellent prognosis ( https://doi.org/10.1016/j.annonc.2022.04.177 ). Here we present long-term follow up of the experimental cohort and the results of the validation cohort. Methods: We included patients with pathologically confirmed diagnosis of stage II and III colon cancer at Hospital Universitario La Paz. The experimental cohort included patients from October 2016 to September 2020. The validation cohort included patients from October 2020 to August 2021. Our prognostic score assigns 1 point for each of the following features: T4, N2, R1 and high tumor budding. Patients with a score of 0 as compared to those with ≥1 had an excellent prognosis regardless AJCC TNM staging. We assess the time to recurrence (TTR) between both groups in the experimental and validation cohort. Results: Baseline characteristics of the experimental cohort (n = 304) were reported previously. 135 (44%) and 169 (56%) patients had a score of 0 and ≥1, respectively. After a median follow up of 45 months, 81 recurrences and 96 deaths were observed. Median TTR was not reached in either cohort (score 0 vs ≥1; P &lt; 0.001), with a hazard ratio (HR) for recurrence of 0.13 [confidence interval (CI)95%: 0.05 to 0.32; P &lt; 0.001]. At 24 months, 95% and 73% of the patients were recurrence free in the score 0 and ≥1 groups, respectively. Within the validation cohort (n = 86), thirty-eight (44%) patients had a score of 0 and 48 (56%) of ≥1. After a median follow up of 19 months, 14 recurrences were observed, all of them in patients with score ≥1. Mediant TTR was not reached in either cohort (P &lt; 0.001), with a HR for recurrence of 0.14 (IC95%: 0.00 – 1.07, P = 0.05). At 12 months, 100% and 78% of the patients were recurrence-free in the score 0 and ≥1 groups, respectively. When assessing TTR according to AJCC TNM stage, we found similar TTR between patients with stage II (n = 45) and III (n = 41) (not reached in either cohort; P = 0.16), with a HR for recurrence of 0.47 (CI95%: 0.15 to 1.40; P = 0.17). At 12 months, 90% and 86% of the patients with stage II and III were recurrence-free. Conclusions: In this study, we validate a prognostic score that identifies a subgroup of patients with localized colon cancer with an excellent prognosis regardless of their TNM stage.
Twitterchats as a means to educate patients with CRC and caregivers and stimulate collaborations.
Authors: Manju George, Aparna Raj Parikh, Jonathan M. Loree, Nina Niu Sanford, Krishan Jethwa
Journal: Journal of Clinical Oncology (2023)

255 Background: During the COVID-19 pandemic, Twitter has been instrumental in accelerating knowledge dissemination and forging collaborations within the medical community and amongst patient advocates. Tweetchats within Twitter are scheduled conversations on a specific topic. In oncology, Tweetchats have been used by cancer advocates to spread awareness and for patient and caregiver education. A colorectal cancer (CRC) specific tweetchat did not previously exist. This abstract describes the creation, and experiences with a CRC specific tweetchat. Methods: The #CRCTrialsChat tweetchat was created by a patient advocate for colorectal cancer patients, caregivers and clinicians to meet and exchange clinical trial-related information. Two gastrointestinal (GI) medical oncologists and two radiation oncologists were enlisted as moderators. The topic for each session is chosen by the patient advocate, who creates an outline and divides the content, which is designed to last a one hour session. The idea is to create engaging, technical, but easy to understand content. Each moderator then works on the answers to their assigned section, which is edited to fit tweet character limit. Sessions may also have guest moderators with expertise on a specific topic. Through tweeting, moderators answer specific questions that come up during the session and later. Results: To date, we have had four sessions covering the following topics: Clinical trial basics, CRC Updates from ASCO22, ClinicalTrialFinders and BRAF-mutated tumors. The content created has been simple and engaging, the format has functioned smoothly, and the reach of #CRCTrialsChat has been steadily increasing. After the most recent session on BRAF in September 2022, the @CRCTrialsChat has 281 followers, 17K impressions and 14.6K profile visits, a reflection of its excellent content. From a clinician perspective, this is a great format to interact with colleagues, discuss enrolling trials and also become familiar with using Twitter. Conclusions: A CRC clinical trial focused tweetchat is an engaging way to deliver trial-related content to an audience of clinicians, patients and caregivers. The current format appears to be an effective way to create and disseminate information. Future sessions will focus on ctDNA, molecular markers such as KRAS and HER2, and rectal cancer trials. Our hope is that #CRCTrialsChat will stimulate continued patient and clinician engagement, increase awareness of clinical trials, enhance trial participation and initiate patient-centric research and collaborations.
The influence of procedural volume on the outcome of endoscopic submucosal dissection for gastric neoplasm: A nationwide population-based study.
Authors: Jae Gyu Kim, Jae Yong Park, Beom Jin Kim, Mi-Sook Kim
Journal: Journal of Clinical Oncology (2023)

285 Background: Endoscopic submucosal dissection (ESD) is a well-established treatment modality for gastric neoplasms. The aim of this study was to investigate the effect of procedural volume on the outcome of endoscopic submucosal dissection (ESD) for gastric cancer or adenoma. Methods: Patients who underwent ESD for gastric cancer or adenoma from November 2011 to December 2017 were identified using the Korean National Health Insurance Service database. Operational definitions to identify target population and post-procedural complications were created by combining the diagnosis and procedure codes, and validated using individual hospital medical record data. The outcomes were the occurrence of post-procedural complications (bleeding, perforation, pneumonia, and 30-day mortality) and additional resection within 180 days after the initial ESD procedure. Hospital volume was categorized into four groups based on the mean annual number of procedures: very high-, high-, low-, very low-volume hospitals (VHVH, HVH, LVH, VLVH). The outcome of ESD was compared in relation to hospital volume. Results: There were 95,411 procedures in 89,780 patients during the study period. There were 5,607 composite events, which included 5,098 bleeding, 601 perforation, and 712 pneumonia cases, respectively. Additional resection within 180days occurred in 7,900 cases. There were significant differences in ESD-related adverse outcomes among the four hospital volume categories. Multiple logistic regression revealed that VHVH, HVH, and LVH were associated with significantly lower relative risk of composite outcome, when compared to VLVH. Similar tendencies were also shown in terms of bleeding, perforation, and pneumonia. This volume-outcome association was not evident in additional resection. Conclusions: Hospital volume was closely associated with adverse clinical outcome in patients with ESD for gastric cancer or adenoma. The outcomes of gastric ESD should be closely and systemically monitored to ensure the safety of patients. [Table: see text]
Primary results of the ICONIC phase 2 trial of perioperative FLOT plus avelumab (FLOT-A) in operable oesophagogastric adenocarcinoma (OGA).
Authors: Anderley Gordon, Benjamin Challoner, Avani Athauda, Andrew Woolston, Sonia Mansukhani, Matt Dunstan, Nikoletta Petrou, Komel Khabra, Retchel Lazaro-Alcausi, Richard Crux, Victoria Borja, Ruwaida Begum, Isma Rana, Sheela Rao, Sacheen Kumar, David Cunningham, Ian Chau, Naureen Starling, M. Asif Chaudry, Marco Gerlinger
Journal: Journal of Clinical Oncology (2023)

446 Background: ICONIC evaluated 4+4 cycles of FLOT-A (2-weekly standard FLOT with 10mg/kg of the anti-PDL1 antibody avelumab) for perioperative treatment of early-stage OGA. We report R0 resection rates, pathologic complete response rates (pCR), pathologic tumour regression grades (TRG) according to Mandard classification and progression free survival (PFS) data in the modified intention to treat population (mITT), and translational analyses. Methods: ICONIC is a single-arm phase II trial of FLOT-A in patients (pts) with ≥cT2-4 or N+ OGA. The pCR rate in surgical specimens was the primary endpoint. Response evaluation according to Mandard, R0 rates and PFS were among secondary endpoints. PD-L1 expression was assessed according to the combined positive score (CPS) with the 22C3 pharmDx kit. Results: The trial closed early after the pCR rate was 15% (95% CI: 49%-83%) once 34 pts in the mITT population (defined as pts who had 1-4 cycles FLOT-A and surgery) as the pre-specified aim to demonstrate a pCR rate of 25% in 40 pts was unlikely to be met. Baseline characteristics of the mITT population were: median age 64y, 79% male, 79% OG junction, 6% oesophageal, 15% stomach, 65% poorly differentiated, 79% T3/4, 59% N+. 91% of pts received all 4 pre-operative cycles and 97% of pts achieved R0 resections. PDL1 CPS ≥1 and CPS ≥5 were nevertheless associated with increased TRG3 and decreased TRG4/5 rates. 3/34 pts (9%) had hypermutated/MMRd tumours and after their exclusion, the association of higher CPS with better TRG3 and decreased TRG4/5 remained. With a median follow up duration of 15.8 months the 12-month PFS was 93.1% (95% CI: 75.1%-98.2%) which is promising compared to historic results with peri-operative FLOT. Conclusions: Although FLOT-A failed to increase pCR rates to 25%, there is a trend towards higher TRG3 and lower TRG4/5 in pts with PDL1 CPS≥1 and CPS≥5 and promising PFS indicate activity of immunotherapy in combination with FLOT chemotherapy. Translational and biomarker analyses by exome- and RNA-sequencing, and multiplex immune cell staining are ongoing and will be reported. Clinical trial information: NCT03399071 . [Table: see text]
First-line chemotherapy regimens associated with survival in advanced pancreatic cancer: A Mexican single-center, real-world study.
Authors: Marytere Herrera, Andrea Maliachi Diaz, Consuelo Diaz, Veronica Salais Michaus, Erika Ruiz, Sebastian Garcia, Sayako Miyagui Adame, German Calderillo Ruiz
Journal: Journal of Clinical Oncology (2023)

683 Background: Effectiveness of FOLFIRINOX and Gemcitabine – Nabpaclitaxel as first-line chemotherapy regimens in advanced pancreatic cancer has been demonstrated in phase III clinical trials. However, prospective studies directly comparing both interventions are lacking. Gemcitabine has proved effective when combined with other drugs such as Oxaliplatin. Despite GEMOX has not proved overall survival benefit over Gemcitabine and it is unclear if its effectiveness could be similar to FOLFIRINOX or Gemcitabine-Nabpaclitaxel, it is broadly used as first line chemotherapy in our center due to safety concerns and higher costs associated to FOLFIRINOX and Nabpaclitaxel. Methods: We retrospectively analyzed data of patients with stage IV Pancreatic Adenocarcinoma treated at Instituto Nacional de Cancerología from 2014 to 2021. Our aim was to compare Overall Survival (OS) in patients treated with GEMOX, FOLFIRINOX, Gemcitabine-Nabpaclitaxel, or Gemcitabine in the front-line setting. Progression Free Survival (PFS), Overall Response Rate (ORR) and Adverse Effects (AEs) were also assessed. Results: A total of 141 patients were analyzed, 72 (51.0%) were treated with GEMOX, 13 (9.2%) with FOLFIRINOX, 9 (6.4%) with Gemcitabine-Nabpaclitaxel and 47 (33.3%) with Gemcitabine. Median Overall Survival for each regimen was: 11.0, 10.7, 6.7 and 4.7 months; (p = 0.078), and median PFS was 9.2, 6.5, 5.7 and 4.0 months, respectively (p = 0.026).ORR was 21.6%, 20.0%, 11.1%, 4.8% with GEMOX, FOLFIRINOX, Gemcitabine-Nabpaclitaxel and Gemcitabine, respectively. The percentage of patients who received a second line chemotherapy after progression was 43.1%, 61.5%, 55.6% and 23.4%, (p = 0.031). Regarding AEs, G3/4 most common effects ( &gt; 5%) were Neutropenia (9.8%, 30.0%, 55.6%, 4.8%; p = 0.001), Diarrhea (2.0%, 10.0%, 11.1%, 0.0%; p = 0.247), and Increased Liver Enzymes (7.8%, 20.0%, 0.0%, 4.8%; p = 0.371). Grade 1/2 Neuropathy was found in 43.1%, 60.0%, 44.4% and 9.5%, p = 0.018. The percentage of patients who required GCSF was 9.8%, 60.0%, 22.2% and 9.5%, P = 0.001. Conclusions: In patients with advanced pancreatic cancer treated with different chemotherapy regimens, median OS was similar in this real-world analysis. Though PFS was higher in the group of patients treated with GEMOX, a higher percentage of patients initially treated with FOLFIRINOX or Gemcitabine – Nabpaclitaxel reached 2nd line chemotherapy after progression. Percentage G3/4 Neutropenia, G1/2 Neuropathy and use of GCSF were significantly higher in patients treated with FOLFIRINOX.
FGFR2-amplified gastroesophageal adenocarcinoma is a distinct genomic class: Lessons learned from a liquid biopsy platform.
Authors: Bushra Shariff, Reagan Barnett, Farshid Dayyani, Steven Brad Maron, Samuel J Klempner, Jude Masannat, Leylah Drusbosky, Rory Mcgriskin, Rutika Mehta
Journal: Journal of Clinical Oncology (2023)

429 Background: Gastroesophageal cancers (GECs) are the 2 nd highest cause of cancer mortality globally. Biomarkers such as MMR, PD-L1, and HER2 are critical for treatment strategies. Emerging biomarkers in late-stage clinical development include FGFR2b. Approximately 30% of GECs express FGFR2b, which is associated with a poor prognosis. FGFR2 amplification ( FGFR2 amp ) is seen in a subset of patients and may be particularly responsive to FGFR2-targeted approaches. We sought to elucidate the genomic landscape of FGFR2 amp GECs using a ctDNA platform. Methods: We retrospectively queried the Guardant Health database from 2017-2022 for patients with advanced GECs who had ctDNA NGS (Guardant360, Redwood City, CA) performed as part of clinical care. Co-alterations were evaluated for patients who harbor FGFR2 amp vs those without FGFR2 amp detected via ctDNA. Fisher’s exact test was used for group comparisons. Results: Approximately 7100 patients met the diagnosis criteria. FGFR2 amp was detected in 263 patients (3.7%). The majority were males (66 and median age in the cohort of FGFR2 amp patients was 66 years (range 22-81 yrs). Most amps were high (+++) in gastric and GEJ (plasma CN≥4) and more frequently observed in patients who are tested at diagnosis (44%) vs progression (19%) (p=0.0147). The mean VAF across samples with high-level FGFR2amp is 22.42%. Patients with FGFR2 amp were enriched for EGFR co-occuring amplifications and cell cycle pathway alterations. CDH1 was frequently mutated in pts under 50 who harbor FGFR2 amp (p=0.0028). Thirty nine percent of patients with FGFR2 amp were also found to harbor a gene fusion and 14% of patients with FGFR2 amps harbored an activating fusion in FGFR1/2/3. Conclusions: FGFR2 is a validated target in GECs, and the contexture of FGFR2 amp will be important to defining patient subgroups with responses to FGFR2-directed therapy. Here we define the FGFR2 amp landscape which may help inform future combination strategies for this emerging biomarker.[Table: see text]
Trial in progress: Phase II study of niraparib and dostarlimab for the treatment of germline or somatic homologous recombination repair mutated metastatic pancreatic cancer.
Authors: Robert R. McWilliams, Pashtoon Murtaza Kasi, Nathan R. Foster, Mojun Zhu, Ryan Michael Carr, Wen Wee Ma, Mindy L. Hartgers, Kayla M. Jones, Jacqueline M. Bartusiewicz, Haidong Dong, Svetomir Markovic, Steven R Alberts, Daniel H. Ahn, Hani M. Babiker, Tanios S. Bekaii-Saab, Fergus Couch
Journal: Journal of Clinical Oncology (2023)

TPS780 Background: Pancreatic adenocarcinoma is an aggressive malignancy with a limited number of therapeutic options. One subset of patients (up to 15%) carries germline and/or somatic mutations in homologous recombination repair genes, most notably BRCA1, BRCA2 and PALB2 amongst others, that confer sensitivity to PARP inhibition. Combinations of PARP inhibitors with anti-PD1 immunotherapy have shown activity in breast and ovarian cancer and have not yet been thoroughly studied in pancreatic cancer. Methods: We designed a single-arm phase 2 investigator-initiated study utilizing the combination of niraparib, a highly selective PARP inhibitor and a dostarlimab, an anti PD1 antibody, in the subset of pancreatic cancer patients with germline or somatic mutations in BRCA1/2, PALB2, BARD1, RAD51C, or RAD51D. Additional inclusion criteria include metastatic pancreatic adenocarcinoma, receipt of a platinum agent in 1st or 2nd line unless contraindicated, and at least 1 but not more than 2 prior lines of systemic therapy not including maintenance. Prior PARP inhibition is allowed, but not immediately prior to enrollment. Exclusion criteria include active unstable autoimmune disease or prior malignancy requiring active treatment within 2 years. Patients are treated with niraparib 200 mg orally once daily on days 1 through 21 of a 21 day cycle. Dostarlimab is administered IV 500 mg every 3 weeks for the 1st 4 cycles and then 1000 mg IV every 6 weeks subsequently. The primary endpoint of the study is the disease control rate at 12 weeks using standard iRECIST criteria. Twenty patients will be enrolled to ensure 19 evaluable. The design has 80% power to detected improvement in disease control rate from 25-50% with significance level of 0.10. Descriptive factors include gene mutated for inclusion, germline/somatic, and platinum refractoriness. Given the size of the study along with genetic heterogeneity there will be no interim analysis. Patients are being enrolled at 3 Mayo clinic sites in Rochester Minnesota, Phoenix Arizona, Jacksonville Florida. To date, 13 patients have been enrolled across all 3 sites. Full accrual is anticipated by early 2023. Correlative studies include genomic characterization of baseline tumors, assessment of immune infiltration of tumor microenvironment, tumor collection for organoid/xenograft, and serial circulating cell-free DNA and immune biomarkers. Trial Identifiers: NCT04493060, Mayo: MC1841. Supported by Glaxo Smith Kline. Clinical trial information: NCT04493060 .
Patterns of pancreatic enzyme replacement therapy (PERT) use among U.S. patients with pancreatic cancer.
Authors: Trang Quynh Dang, David D. Stenehjem, Arjun Gupta
Journal: Journal of Clinical Oncology (2023)

696 Background: PERT is an important but costly and inconsistently used supportive care medication in PC. We sought to characterize patterns of PERT use among U.S. insured patients with PC. Methods: We conducted a retrospective observational analysis of patients with a primary diagnosis of pancreatic adenocarcinoma in the IBM MarketScan national claims database between 2013-2019. We identified pharmacy claims for PERT (Creon, Pancreaze, Pertzye, Viokace, and Zenpep) and classified patients as PERT-users (≥ 1 PERT prescription [Rx]) and non-PERT users. We used descriptive statistics for clinical, demographics, and costs. Multiple logistic regression identified predictors of PERT use. Kaplan-Meier method assessed time from PC diagnosis to first PERT Rx. Results: Of 19,866 patients with PC (median age 62 years, 49% women), 6,918 (35%) were PERT-users. The median follow-up was 11 months (PERT users: 14 months, non-PERT users: 9 months). Overall, 43% of patients received no cancer-directed treatment. PERT-users were more likely to have a history of pancreatitis (acute, odds ratio [OR] = 1.9; chronic, OR = 3.6), and received chemotherapy (OR = 1.2), surgery (OR = 2.3), and radiation (OR = 1.4). Among all PERT-users, the median time from PC diagnosis to first fill was 1.9 months (95% CI: 1.8,2.0). The median time from surgery to first fill was 1.6 months (95% CI: 1.4,1.7). The median number of PERT Rxs was 4; 22% of PERT-users received 1 Rx. A median of 150 days of PERT was supplied across all Rxs per patient. The median (IQR) cost of each PERT Rx was $25 ($0- $50). PERT accounted for 16% of all drug out-of-pocket costs (OOPC) (excluding systemic outpatient cancer-directed treatment), and 7% of all healthcare OOPC. Patients with PERT had significantly higher monthly OOPC on Rxs but lower on all other services, including inpatient and outpatient services (all p &lt; 0.0001). Overall, PERT-users had significantly lower per-patient per-month (PPPM) OOPC vs non-PERT users ($469, vs $520, p &lt; 0.0001). They also had fewer PPPM outpatient (0.7 vs 1.2, p &lt; 0.0001) and ER (0.4 vs 0.5, p &lt; 0.0001) visits. Conclusions: In this national study of insured U.S. adults with PC, only one-third received PERT. Of those receiving PERT, approximately a fifth received just a single Rx. PERT users, despite higher OOP drug spending had reduced overall OOP costs and fewer healthcare visits. These data highlight the need to explore non cost-related reasons for lack of and ways to standardize PERT use.